Obsessive compulsive disorder (OCD) is ranked by the World Health Organization as one of the top 20 disabling illnesses in terms of lost income and diminished quality of life. Many OCD patients respond well to treatment with serotonin reuptake inhibitors (SRIs);however 20% to 40 % of OCD patients are resistant to SRIs, and is believed that abnormalities in neurotransmitter systems other than serotonin may be responsible for OCD symptoms in these patients. This study proposes to measure neurotransmitter profiles (consisting of 3 substances with neurotransmitter properties accessible by advanced magnetic resonance spectroscopy (MRS) techniques) - glutamate (Glu), 3-aminobutyric acid (GABA), and N- acetyl aspartyl glutamate (NAAG). It is hypothesized that SRIs resistant OCD patients will have lower levels GABA (an inhibitory neurotransmitter), higher levels of Glu (an excitatory neurotransmitter (Glu), and lower levels of NAAG (a precursor of Glu) as compared to treatment responders, or control subjects. Measurements will be made in 2 key brain regions in OCD: anterior cingulated (ACC), combined basal ganglia and thalamus (BG-TH) at 3T using state-of-the-art spectral-editing MRS techniques. In total 48 subjects will be studied over 2 years, 16 controls, 16 OCD responders and 16 OCD non-responders. This proposal promises to improve understanding of the role of the glutamatergic and GABAergic systems in OCD patients and, in the long term, may lead to the development of new therapeutic strategies for OCD. PUBLIC HEALTH RELEVANCE: Twenty to 40 % of obsessive-compulsive disorder (OCD) patients are resistant to treatment with serotonin reuptake inhibitors (SRIs). We sought to explore the role of the Glutamatergic and 3-aminobutyric acid (GABAergic) neurotransmitters in 2 brain regions of the brain in OCD and to correlate it to treatment resistance. In the long term, this research may lead to a better understanding of schizophrenia and treatment approaches.